Salicylic Acid-Catalyzed One-Pot Hydrodeamination of Aromatic Amines by tert-Butyl Nitrite in Tetrahydrofuran

Article abstract of DOI:10.1002/adsc.201700475

A significant acceleration in the hydrodeamination of in situ formed diazonium salts (from aromatic amines) has been observed in the presence of 10-mol% salicylic acid, using tetrahydrofuran as the hydrogen donor. The reaction proceeds efficiently at 20 °C for a wide range of substituted anilines, even at 10-mmol scale, without any other additive. The same protocol has been adapted to the selective deuterodeamination of some aromatic amines. Control experiments clearly show that aryl radicals are involved in the reaction mechanism. (Figure presented.).

Full text of DOI:10.1002/adsc.201700475

Title: Salicylic Acid-Catalyzed One-Pot Hydrodeamination of Aromatic
Amines by tert-Butyl Nitrite in Tetrahydrofuran
Authors: Diego Felipe-Blanco, Francisco Alonso, and Jose Gonzalez-
Gomez
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700475
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Advanced Synthesis & Catalysis
10.1002/adsc.201700475
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Salicylic Acid-Catalyzed One-Pot Hydrodeamination of
Aromatic Amines by tert-Butyl Nitrite in Tetrahydrofuran
a
a
a,
Diego Felipe-Blanco, Francisco Alonso, and Jose C. Gonzalez-Gomez *
a
Instituto de Síntesis Orgánica (ISO) and Departamento de Química Orgánica, Facultad de Ciencias, Universidad de
Alicante, Apdo. 99, 03080 Alicante, Spain.
E-mail: josecarlos.gonzalez@ua.es
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract.
A
significant
acceleration
in
the would give access to regioselectively deuterated
hydrodeamination of in situ formed diazonium salts (from aromatic compounds. The latter compounds play
aromatic amines) has been observed in the presence of 10- important roles in the elucidation of reaction
[
14]
mol% salicylic acid, using tetrahydrofuran as the hydrogen mechanisms,
as well as in the investigation of
[15]
donor. The reaction proceeds efficiently at 20 ºC for a wide biosynthetic pathways.
range of substituted anilines, even at 10-mmol scale,
without any other additive. The same protocol has been
adapted to the selective deuterodeamination of some
aromatic amines. Control experiments clearly show that
aryl radicals are involved in the reaction mechanism.
Some of the above mentioned methods require
water or alcohols to solubilize NaNO2, the reaction of
which with the intermediate diazonium salt gives rise
to undesirable phenols or ethers. In addition, the low
solubility of inorganic salts in organic solvents is
usually overcome with the use of a large excess of
reagents and solvents, which clearly reduces the
feasibility of the protocol. It is also worth noting that
electron-donating groups significantly retard the
reaction and many of the developed methods fail for
Keywords: hydrogen transfer; radicals; aromatic amines;
isotopic labelling; sustainable chemistry
[4]
this subclass of substrates. In principle, we found
the use of alkyl nitrites in organic solvents attractive
because some of the aforementioned limitations can
be minimized. In this regard, the only one-pot
Introduction
[11]
[10]
procedures described make use of DMF or THF
at 65 ºC (Scheme 1a and 1b). Given the commercial
Anilines are highly activated substrates for
electrophilic aromatic substitutions, and the
subsequent removal of the amino group is a well-
known strategy to exploit its activating and directing
effect in the synthesis of aromatic compounds.
Typically, this transformation is achieved by the
availability of [D
compared to DMF,
8
]-THF and its lower toxicity
[16]
we reasoned that the use of
alkyl nitrites in THF at 20–25 ºC, under almost
neutral conditions, would be a more convenient
protocol for the reductive deamination of anilines
initial
arenediazonium
hydrodediazotization.
formation
of
the
corresponding
by
(
Scheme 1c).
salt,
followed
a
A
plethora of reductive
[1]
protocols have been implemented with this purpose,
involving different hydrogen donors, namely:
[2]
[3]
[4]
[5]
alcohols,
HPO
3
,
NO/THF,
Et
3
N,
catalytic
Fe(II) in DMF,[ and trichlorosilane. Recently, a
visible-light promoted reaction catalyzed by Eosin B
in DMF has also been reported.[ One common
drawback in most of the existing methods is that they
rely on the isolation of unstable aryl diazonium salts.
In this context, a more limited number of one-pot
procedures have been developed, including: (a) the
6]
[7]
8]
[9]
use of NaNO
2
in H
3
PO
2
,
(b) the reaction with alkyl
[
10]
[11]
nitrites in THF or DMF at 65 ºC, (c) NaNO
2
in
and recently,
O.[ Importantly, the use
of a deuteride equivalent as the hydrogen source
Scheme 1. One-pot procedures in anhydrous media for the
hydrodeamination of anilines.
[12]
AcOH/H
2
O followed by NaHSO
3
,
13]
NaNO /AcOH in CHCl
2
3
/H
2
1
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Advanced Synthesis & Catalysis
10.1002/adsc.201700475
Recently, Carrillo and co-workers demonstrated
Table 1. Optimization of the reaction conditions.
that in-situ generated arenediazonium ions can be
conveniently reduced to aryl radicals at room
temperature, using substoichiometric amounts of
[
17]
[18]
ascorbic acid (AscH
2
)
or gallic acid
as
promoters. The AscH
2
protocol has been
implemented for the radical C-H arylation of
[19]
(
hetero)arenes in the preparation of aryl sulfides, in
[20]
a [4+2] benzannulation to build phenanthrenes,
and in
a
radical translocation to form -
[21]
alkoxybenzamides. However, to our surprise, the
use of these promoters in a one-pot reductive
deamination of anilines has not been documented so
far.
[a]
Entry
Additive
none
Ascorbic Acid
p-TsOH
(+)-CSA
DMSO
Gallic Acid
Yield (%)
25 (55)
96
[
b]
1
2
3
4
5
6
Results and Discussion
18
73
68
92
100
100
24
Considering the lower reactivity of electron-rich
substrates in the title reaction, we selected p-anisidine
as a model substrate to carry out the reductive
deamination, via diazonium salt, in the presence of
different possible promoters and THF at 20 ºC (Table
[
c]
7
8
Salicylic Acid
Salicylic Acid
Methyl Salicylate
O-Acetyl salicylic Acid
[
d]
9
1
). The reaction worked poorly in the absence of
1
0
41
additives at 20 ºC and a moderate yield was obtained
at 65 ºC (entry 1), probably through in-situ formed
diazo anhydrides (Ar-N=N-O-N=N-Ar) and their
radical fragmentation.[ However, the addition of 10
mol-% of ascorbic acid, gallic acid, or salicylic acid
[
a]
Yield determined by GC with phenanthrene as the
internal standard in 0.3 mmol-scale reactions.
22]
[b]
At THF reflux.
[
c]
Using 1:1 THF/H
obtained.
2
O as solvent, 50% yield of 2a was
(
entries 2, 6 and 7) significantly enhanced the
[
d]
reaction, leading to anisole in excellent yield after 3 h
of reaction. Additives such as (+)-CSA
Protected from light. CSA = camphorsulfonic acid.
(
camphorsulfonic acid) or DMSO (dimethyl
sulfoxide) had a moderate positive impact on the
reaction. We have not found any precedent in the
literature for the use of salicylic acid to promote the
generation aryl radicals. Thus, we focused our
attention on this catalyst because: (a) it is inexpensive
functionalities was tolerated, including ethers,
esters, ketones, halogens, nitro, nitriles, alkyl, aryl,
and trifluoromethyl. Remarkably, free carboxyl and
hydroxyl groups at the para- position were also found
to be compatible with this procedure (products 2b
and 2c). In other related methods, anilines bearing
free hydroxyl groups afforded the corresponding
(
59 €/1 Kg, Sigma-Aldrich); (b) it is non-toxic in low
doses (an active metabolite of aspirin); and (c) it is a
renewable feedstock (a plant hormone derived from
salicin). It is known that household compact
fluorescent lamps (CFL >360 nm) allow the
generation of aryl radicals from aryldiazonium salts
under catalyst free conditions.[ For this reason, we
confirmed that a quantitative yield was also obtained
when the mixture of our model reaction was
protected from light (entry 8). Interestingly, both
hydroxyl groups need to be free in the promoter in
order to maximize the yield. For instance, the
addition of methyl salicylate (entry 9) had no effect
on the background reaction (entry 1) and a poor
acceleration was observed in the presence of O-acetyl
salicylic acid (entry 10).
[10, 12]
deaminated products in very low yields,
or did
[8]
not react at all; this behavior could be likely due to
azo coupling or other side reactions based on the
nucleophilicity of the OH group. In contrast, the
hydroxyl group at the ortho- position completely
inhibited the reaction with our developed protocol.
We speculated that the nitrosation step could be more
difficult for this substrate, where an intramolecular
hydrogen-bond might protect the amino group from
the reaction with electrophiles. Despite iodine
transfer is a well-known process in aryl radical
23]
[24]
chemistry,
iodine-bearing anilines afforded the
corresponding products in moderate-to-good yields
[2h (from o-, m- and p-iodoaniline) and 2u]. This
results suggest that if aryl radicals are involved, the
hydrogen abstraction from THF should be faster than
the iodine transfer. The protocol was also examined
with different heteroaromatic amines to produce the
heterocycles 2p, 2q, and 2t in moderate yields.
Pyrimidine (2r) was also obtained, but in a lower
yield, presumably because of the high electrophilicity
of the intermediate diazonium ion. Moreover, the
reaction was scale up to 5 mmol for some substrates,
With the optimized conditions in hand, we next
explored the scope and limitations of the developed
protocol with different anilines (Table 2). We
screened diverse substituted anilines with electron-
donating and electron-withdrawing groups. The
products were obtained in synthetically useful yields
regardless the electronic nature of the substituent,
ranging from moderate to excellent. Giving the mild
conditions used, a variety of substituents and
2
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Advanced Synthesis & Catalysis
10.1002/adsc.201700475
Table 2. Substrate scope of aromatic amines.[a]
[
a]
GC yields vs. phenanthrene from 0.3 mmol of 1 (in parentheses the yields of isolated pure products from 5 mmol of 1).
The H atom in red indicates the original position of the amino group in the starting amine.
[
[
b]
c]
7
3% yield of isolated pure product for a 5 mmol-scale reaction.
8
2% yield of isolated pure product for a 5 mmol-scale reaction.
giving rise to the pure products (2d, 2k, 2p, 2s, 2t and
u) in good-to-excellent isolated yields. It is also
2
noteworthy that significantly higher yields were
obtained for some substrates which were reported to
react under refluxing THF without any catalyst (e.g.
p-1b, o-1h and p-1k).[
10]
In order to test the applicability of this protocol at a
larger preparative scale, we performed the
hydrodeamination with 10 mmol of the substrate 1v.
Following the standard procedure in a gram-scale,
product 2v was obtained in good yield after
purification (Scheme 2). We must highlight that
aniline 1v was prepared by nitration from p-anisidine
Scheme 2. Gram-scale hydrodeamination reaction.
We next examined the feasibility of this protocol
for the deuterodeamination of aromatic amines using
[D ]-THF as solvent. In this case, the standard
8
[25]
(
in three steps) following a reported procedure, the
procedure was slightly modified to utilize lower
amounts of the deuterated reagent and the reactions
were run in 0.5 M solutions for 2 h. As shown in
Table 3, six anilines were selected for this study from
the previous examined substrates (Table 2) taking
hydrodeamination of which also demonstrates the
potential of this method to use the amino
functionality as a traceless directing group in S Ar.
E
3
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Advanced Synthesis & Catalysis
10.1002/adsc.201700475
into account their diverse functionalization and the
low volatility of the products. In all cases, the
incorporation of deuterium was excellent, obtaining
1
compounds with  97:3 D/H ratio, according to H-
NMR. It is worth mentioning that in many reported
arene deuteration protocols, other competitive H-
transfer processes take place efficiently, resulting in
[26]
lower isotope incorporation.
Although the yields
obtained for the deuterated products were uniformly
slightly lower than those for the hydrogenated
counterparts, reasonable yields for isolated pure
deuterated compounds were obtained (4281%) in
only 2 h at 20 ºC.
Table 3. Deuterodeamination reaction with [D
8
]-THF.[a]
Scheme 3. Control experiments for mechanistic studies.
Given the above mentioned control experiments
and inspired by mechanistic investigations previously
[17-21]
reported,
we have proposed
a
plausible
[
a]
mechanism for this reaction (Scheme 4). The fact that
O-acetyl salicylic acid has a moderate positive impact
on the reaction, while methyl salicylate does not act
as catalyst suggested that the carboxylate is directly
involved in the reaction. Considering the reported
redox potentials for the reduction of diazonium salts
Yields are reported for isolated pure products from 0.3
mmol of 1. The percentages of deuteration were
determined by H-NMR.
1
We performed some control experiments to gain an
insight into the reaction pathway. As shown in
Scheme 3a, we were able to recover most of the
salicylic acid used as catalyst (GC-MS determination)
by aqueous workup, once the hydrodeamination of 1a
was finished. In order to show the intermediacy of
aryl radicals, we performed the deamination of p-1i in
[29]
(
Ered  0 V vs Ag/AgCl)
and oxidation of
[30]
salicylates (Ered  + 1.1 V vs Ag/AgCl), a single
electron transfer (SET) between these species seems
unreasonable as the initiation step because it is an
endergonic reaction (E   1 V). Therefore, we
propose that the in-situ formed diazonium salt I is
protonated by salicylic acid and undergoes a
nucleophilic addition of salicylate through the
carboxy group. The aryl diazobenzoate intermediate
CH CN (to minimize H-abstraction) using 2,2,6,6-
3
tetramethylpiperidinyl-1-oxy radical (TEMPO) as a
radical trap (Scheme 3b);[27] adduct 3 was isolated in
[31]
II could easily decompose to generate N
2
,
the aryl
5
6% yield after purification. Additionally, when a
radical (trapped with TEMPO and with iodoacetic
acid) and salicyloyl radical (likely stabilized by an
intramolecular H-bond). While further experiments
are required to support this proposed mechanism, we
have also confirmed that the reaction is not promoted
by visible-light (CFL lamps; Table 1, entry 8) and
occurs under very mild thermal activation (20 ºC).
The aryl radical could rapidly abstract a hydrogen
solution of the substrate p-1g and 2-iodoacetic acid in
CH CN was treated with salicylic acid (10 mol-%)
3
and t-BuONO, 4-bromoiodobenzene was isolated as a
pure solid in 52% yield (Scheme 3c), suggesting the
formation of 4-bromophenyl radical.[28] Furthermore,
when equimolar amounts of THF/[D ]-THF were
8
used under our standard conditions for the
hydrodeamination of 1v, a 27% of deuterium
incorporation was observed in product 2v at the
initial stage of the reaction (Scheme 3d). The large
KIE obtained (k
abstraction from THF is the rate-determining step of
the reaction.
6
-1 -1
[32]
atom (HAT) from THF (k~10 M s at 25 ºC) to
form the product and the α-tetrahydrofuranyl radical
IV). The reaction could be propagated through a
(
H
/k
D
= 2.70) suggests that H-
radical-chain mechanism where the aryl diazonium
salt is reduced by radical IV, regenerating the aryl
radical and forming the oxoniun ion V which,
eventually, would lead to volatile ketal or hemiketal
4
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Advanced Synthesis & Catalysis
10.1002/adsc.201700475
by-products.[33] The oxidation potential of potassium
salicylate (E1/2 = + 1.1 V vs Ag/AgCl) is reported to
be rather low compared with that of the parent
General Procedure for the hydrodeamination reaction
(
Table 2)
The corresponding aniline (0.30 mmol) and the salicylic
acid (4.14 mg, 0.03 mmol) were added to an oven dried
Schlenck. The system was evacuated and filled with argon
[29]
potassium benzoate (E1/2 >1.5 V vs Ag/AgCl). This
suggests that the hydroxyl group at the ortho-position
stabilizes radical III, probably by H-bond
stabilization and a captodative effect of the carboxyl
and hydroxyl groups.[ It seems reasonable that the
turnover of the catalyst (which was isolated in native
form after the reaction) could be produced by single-
electron reduction of III by radical IV.
(
three times) before dry THF (1 mL) was added, and the
reaction mixture was stirred vigorously until
a
homogeneous solution was obtained (5 min aprox.). At this
point, tert-butylnitrite (47 μL, 41.3 mg, 0.36 mmol) was
added (the solution turned orange after some minutes) and
34]
the stirring continued for 3 h, keeping the temperature at
o
2
0 C with a water bath. At this time, water was added (2
mL) and the mixture was extracted with EtOAc (3 × 4 mL).
The organic layers were collected, dried over anhydrous
MgSO
4
and filtered. To this solution was added
phenanthrene (53.4 mg, 0.3 mmol) as the internal standard
(
IS). An aliquot of this solution was injected into a GC
apparatus to determine the reaction yield. Substrates o-1d,
o-1k, 1p, 1s, 1t, and 1u were subjected to this procedure at
5
-mmol scale and 1v at 10-mmol scale, and the
corresponding compounds 2 were isolated in pure form
[
35]
after column chromatography to determine the yields.
General Procedure for the deuterodeamination
reaction (Table 3)
Following the aforementioned general procedure for
selected anilines (o-1j, 1q, 1s, 1t, 1u and 1v), but using dry
8
[D ]-THF (0.50 M), the corresponding [D]-2 compounds
were
obtained
in
pure
form
after
column
[
36]
chromatography.
Supporting Information
Details for experimental procedures, determination of
yields by gas chromatography (Tables S1, S2 and S3),
purification and characterization data of the isolated
compounds are included. Some mechanistic studies,
and NMR spectra ( H- and C-NMR) of the pure
isolated compounds are also included.
Scheme 4. Proposed reaction mechanism.
1
13
Conclusion
In summary, we have reported a convenient one-
pot methodology for the selective hydrodeamination Acknowledgements
of anilines and heteroaromatic amines using THF as
the hydrogen source. The reaction is catalyzed by
salicylic acid (10 mol-%) and takes place at 20 ºC in
We thank the Ministerio de Economia
CTQ2015-66624-P) and the University of Alicante (VIGROB-
73) for financial support.
y Competitividad
(
1
23 h, without any metal additive, stoichiometric
reductant or light induction. Importantly, the reaction
conditions are compatible with the presence of a
variety of functional groups, irrespective of their
electron-donating or –withdrawing character.
Moreover, the method is easily scalable up to 10
mmol-scale. Remarkably, the use of commercial
References
[
1] N. Kornblum, Org. React., 1944, 2, 262.
[2] a) H. T. Clarke, E. R. Taylor, Org. Synth. Coll. 1941, I,
415; b) A. H. Blatt, Org. Synth. Coll., 1950, II, 592.
[
D ]-THF allowed the selective deuterodeamination
8
of aromatic amines with excellent isotopic purity of
the products. Mechanistic studies revealed that aryl
radicals are reaction intermediates and that the
hydrogen transfer from THF is a rate-limiting step of
the reaction. We hope that the use in this report of the
underexploited salicylic acid as catalyst, to facilitate
the formation of aryl radicals, will find future
synthetic applications. We are currently working on
new sustainable methods to expand the application of
this concept.
[
3] a) N. Kornblum, G. D. Cooper, J. E. Taylor, J. Am.
Chem. Soc. 1950, 72, 3021; b) N. Kornblum, A. E.
Kelley, G. D. Cooper, J. Am. Chem. Soc. 1952, 74,
3
074.
[4] T. Itoh, K. Nagata, Y. Matsuya, M. Miyazaki, A.
Ohsawa, J. Org. Chem. 1997, 62, 3582.
[
[
5] K. H. Park, Y. H. Cho, E. J. Jang, Bull. Korean Chem.
Soc. 1996, 17, 179.
6] F. W. Wassmundt, W. F. Kiesman, J. Org. Chem. 1995,
6
0, 1713.
Experimental Section
5
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201700475
[
[
[
[
[
[
[
[
7] M. Lormmann, S. Dahen, S. Bräse, Tetrahedron Lett.
000, 41, 3813.
[26] For selected examples, see: a) F. W. Wassundt, W. F.
2
Kiesman, J. Labelled Compd. Radiopharm. 1995, 36,
2
81; b) T. Mutsumi, H. Iwata, K. Maruhashi, Y.
8] M. Majek, F. Filace, A. J. von Wangelin, Chem. Eur. J.
015, 21, 4518.
Monguchi, H. Sajiki, Tetrahedron 2011, 67, 1158; c) M.
Rudzki, A. Alcalde-Aragonés, W. I. Dzik, N.
Rodríguez, L. J. Gooßen, Synthesis 2012, 184; d) R.
Grainger, A. Nikmal, J. Cornella, I. Larrosa, Org.
Biomol. Chem. 2012, 10, 3172; e) Ma, G. Villa, P. S.
Thuy-Boun, A. Homs, J.-Q. Yu, Angew.Chem. Int. Ed.
2
9] N. Kornblum, D. C. Iffland, J. Am. Chem. Soc. 1949,
1, 2137.
7
10] J. I. G. Cadogan, G. A. Molina, J. Chem. Soc. Perkin
Trans I, 1973, 541.
2
014, 53,734.
11] M. P. Doyle, J. F. Dellaria, B. Siegfried, S. W. Bishop,
[
[
3
27] Under the standard conditions, but using CH CN as
J. Org. Chem. 1977, 42, 3494.
solvent, only 21% of 2i was obtained.
12] O. J. Geoffroy, T. A. Morinelli, G. P. Meier,
28] a) F. W. Wassmundt, W. F. Kiesman, J. Org. Chem.
995, 60, 1713; b) F. W. Wassmundt, W. F. Kiesman, J.
Tetrahedron Lett. 2001, 42, 5367.
1
13] K. Burglova, S. Okorochenkov, J. Hlavac, Org. Lett.
Org. Chem. 1997, 62, 8304.
2
016, 18, 3342.
[
[
29] H.-H. Yang, R. L. McCreery, Anal. Chem. 1999, 71,
14] E. M. Simmons, J. F. Hartwig, Angew. Chem. Int. Ed.
4081.
2
012, 51, 3066.
30] J. Colucci, V. Montalbo, R. Hernandez, C. Pouullet,
Electrochim. Acta 1999, 44, 2507.
[
[
15] A. Katsnelson, Nat. Med. 2013, 19, 656.
16] D. Prat, A. Wells, J. Hayler, H. Sneddon, C. R.
[31] It is known that acyloxydiazoaryls decompose easily
to generate aryl radicals. For selected examples, see: a)
R. Huisgen, G. Horeld, Liebigs Ann. Chem 1949, 562,
McElroy, S. Abou-Shehada, P. J. Dunn, Green Chem.
2
016, 18, 288.
1
1
1
37; b) C. Rüchardt, B. Freudenberg, Tetrahedron Lett.
964, 5, 3623; c) J. I. G. Cadogan, Acc. Chem. Res.
971, 4, 186. However, we were unable to isolate
[
[
17] F. P. Crisóstomo, T. Martín, R. Carrillo, Angew. Chem.
Int. Ed. 2014, 53, 2181.
intermediate II in pure form and other pathways for the
salicylic acid catalyzed generation of aryl radicals
cannot be ruled out.
18] M. D. Perretti, D. M. Monzón, F. P. Crisóstomo, V. S.
Martín, R. Carrillo, Chem. Commun. 2016, 52, 9036.
[
[
19] M.-j. Bu, G.-p. Lu, C. Cai, Synlett 2015, 26, 1841.
[
[
32] J. Fossy, D. Lefort and J. Sorba, Free Radicals in
Organic Chemistry, John Wiley & Sons, 1995, p 289.
20] M.-j. Bu, G.-p. Lu, C. Cai, Org. Chem. Front. 2016, 3,
6
30.
33] 2-Hydroxytetrahydrofuran (GC-MS included on page
S17 of the Supporting Information) has been detected
by GC-MS in the formation of 2a under the standard
[
[
21] F.-Q. Huang, G.-X. Zhou, X. Dong, L. W. Qi, B.
Zhang, Asian J. Org. Chem. 2016, 5, 192.
conditions.
The
formation
of
2-tert-
22] a) T. Kauffmann, H. O. Friestad, H. Henkler, Liebigs
Ann. Chem. 1960, 634, 64; b) E. Müller, H. Haiss,
Chem. Ber. 1962, 95, 570; c) E. Müller, H. Haiss,
Chem. Ber. 1962, 95, 1255.
butoxytetrahydrofuran, and its subsequent fast
transformation under the GC-MS conditions, cannot be
ruled out.
[
[
[
34] A similar explanation was proposed for the special
stabilization of the galloyl radical. See reference 18.
[
[
23] D. Cantillo, C. Mateos, J. A. Rincon, O. de Frutos, C.
O. Kappe, Chem. Eur. J. 2015, 21, 12894.
35] More experimental details are included in the
Supporting Information file (pages S7-S11).
24] a) J. F. Bunnet, C. C. Waser, J. Am. Chem. Soc. 1966,
8
8, 5534; b) D. L. Brydon, J. I. G. Cadogen, J. Chem.
Soc. C. 1968, 819; c) T. J. Broxton, J. F. Bunnett, C. H.
Paik, J. Org. Chem. 1977, 42, 643.
36] More experimental details are included in the
Supporting Information file (pages S12-S15).
[
25] P. E. Fanta, D. S. Tarbell, Org. Synth. 1945, 25, 78.
6
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